1. Field of the Invention
The present invention relates to plastic bags used for the collection, processing, and storage of blood products, such as plasma. Specifically, the invention relates to an ethylene vinyl acetate bag used in the collection of human plasma, freezing the plasma after collection, storing the frozen plasma, and subsequent processing.
2. Description of Background Art
Current containers used for plasma storage and processing are of two principle types: (1) a polyvinyl chloride (PVC) flexible bag, or (2) a rigid or semi-rigid blow molded olefin bottle or bag.
PVC bags have been used for decades for freeze storing plasma, and have the advantages of efficient manufacturability, low container cost, and good blood compatibility. However, significant disadvantages also exist with this type of container. The most significant disadvantage is the fragility of the container when frozen. The glass transition temperature (Tg), or temperature at which the film changes from flexible to brittle, is higher than the freezing temperatures commonly used for plasma.
This means that the bag is flexible and relatively strong at room temperature, but becomes excessively brittle or glass-like when frozen. This fragility leads to some percentage of the bags breaking during storage and handling. Bag breakage is undesirable since it allows for potential contamination (bacterial, particulate, and the like) that can adversely affect the purity of products subsequently made from this plasma. Bacterial contamination, in particular, can adversely affect protein yields and quality during the fractionation process due to the release of proteolytic enzymes and pyrogens.
The PVC film used in the manufacture of the plasma bags presently on the market has routinely been manufactured using the plasticizer di-2-ethyl-hexyl phthalate (DEHP). Considerable amounts of DEHP are leached from the walls of the blood bags by the plasma during storage. Recently, concern has been raised over the potentially harmful effects of DEHP in blood products chronically transfused to patients.
A common method for removing plasma in a frozen state from PVC storage bags is fracturing the bags at cryogenic temperatures, followed by shucking the bag from the frozen plasma. That process involves dipping the entire bag and contents into liquid nitrogen. The frozen bag then is shattered, for example by dropping the frozen bag onto a surface from a distance. The frozen plasma or blood component then is removed, using a process known as "shucking", from the shattered bag fragments.
During the shucking step, when the bag fragments are removed from the plasma "pellet", often some plasma sample is lost due to adherence to the inside of the bag. The bag, thus, should not adsorb any of the plasma, but should permit the total release of all plasma from the bag walls.
By contrast, olefin bottles and bags typically are break resistant while frozen, but are otherwise difficult to open. Olefin bags do not readily shatter using the liquid nitrogen process described above. The process required to remove plasma from frozen olefin bags and bottles involves the time consuming and cumbersome thawing, or "skin thawing", process. This process involves partially thawing the frozen bag and plasma until the bag lifts away from the plasma surface. This process potentially degrades the desired proteins contained in the frozen plasma. Further, since the olefin bottles are not flexible they require substantial storage space due to bulk of the containers.
Medical solution bags are available on the market that are manufactured from high concentrations of ethylene vinyl acetate. For example, one such bag contains approximately 18% vinyl acetate per total polymer content. However, such bags are not useful for the fracturing process outlined above, since plasma adheres to the walls of the bags. Thus, it is difficult to get a complete extraction of plasma from bags having a high vinyl acetate content, i.e., a content above 18% vinyl acetate per total polymer content, resulting in significant loss of product due to losses of plasma adhering to discarded film fragments.
Ethylene vinyl acetate films with vinyl acetate contents below 9% have suitable plasma release characteristics during the cryogenic fracturing process. However, these films do not readily form into plasma bags since they do not form good radio frequency seals due to the lack of sufficient polarity in the polymer structure. This lack of sufficient molecular polarity is due to the low level of the vinyl acetate component in the film structure. Radio frequency (RF) sealing is the preferred method of bag manufacture due to its known efficiency and ability to produce water-tight, high-pressure seals.
Thus, there remains a need for a safe, effective method and bag for collecting, processing, and storing plasma and other blood protein components that permits complete recovery of the plasma sample from within the bag during a cryogenic fracturing process.